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Antimicrobial resistance (AMR) has diminished the effectiveness of present antibiotics, posing a huge threat to global community health and economic stability. This study investigates the CRISPR-Cas framework's potential as a cutting-edge tactic to fight antimicrobial resistance. Current applications, limitations, and prospective future uses are analyzed. CRISPR antimicrobial strategies, which bring together the latest developments in gene-targeting strategies, engineered delivery platforms, and translational applications to fight multidrug-resistant pathogens. CRISPR technology is different from traditional antimicrobial treatments that target general antimicrobial resistance genes, instead allowing targets to be eliminated specifically by sequence, while retaining beneficial microbial communities, which has the potential to be a transformative precision antimicrobial treatment. Nevertheless, there is still a need for optimization of delivery systems, specificity of targets, biosafety, and regulations to ensure successful clinical translation, especially given their amazing advances. Recent research confirms that CRISPR-based mechanisms also affect different bacterial species, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, playing a key function in averting the emergence of resistance genes in these bacteria. Changes to CRISPR loci affect how resistance genes are targeted in ESKAPE pathogens, and CRISPR-Cas9 successfully lowers resistance by focusing on genes like tetM and ermB. A promising application of CRISPR-Cas systems in combating antimicrobial resistance (AMR) is the precise targeting of plasmid-borne mcr-1 resistance genes and other mobile genetic elements that facilitate the dissemination of colistin resistance. But the efficiency of CRISPR-Cas is diminished in some bacterial strains due to variations in their CRISPR loci. Enhancing transformation approaches and minimizing off-target impacts are critical challenges to confirm the precision and safety of CRISPR-based mechanisms in therapeutic applications. Advances in these areas are likely to continue to enable the development of next-generation CRISPR therapeutics for the effective management of multidrug-resistant bacterial infections.

In 2022, the case of Andrea Prudente, an American tourist denied an abortion for a non-viable pregnancy in Malta, catalysed unprecedented social mobilisation, and compelled a legislative review of the country's abortion ban. This paper traces the political and social dynamics that shaped this process, from the initial advocacy to the final, heavily contested legislative outcome. Drawing on Morgan and Roberts' concept of reproductive governance, we examine media content and parliamentary discourses to trace how state actors mediated the conflict between competing moral, and legal frameworks. Our analysis demonstrates that while persistent pressure by pro-choice advocates was instrumental in forcing a legislative review, the government's initial proposed reforms were systematically contested, and ultimately neutralised by a powerful, well-organised anti-choice countermovement. We argue that state actors ultimately capitulated to immense conservative pressures from influential religious and civil society actors. The resulting amendment, which permits termination only under exceptionally restrictive circumstances to save a pregnant person's life, is a stark example of how reproductive governance can accommodate pressure for change while leaving the underlying system intact. This process highlights how legal reform can be critically decoupled from meaningful access, failing to secure genuine reproductive rights. Despite its profound limitations, the amendment constitutes the first-ever legal exception to Malta's absolute ban, proving that such entrenched governance frameworks are not immutable. The Prudente case and the mobilisation it inspired have irrevocably fractured the previous politico-legal consensus, thereby creating a precedent for future legal challenges and continued advocacy for comprehensive reproductive justice in Malta. In 2022, an American tourist in Malta named Andrea Prudente needed an abortion for a pregnancy that could not survive. Doctors refused because of the country's total ban. Her case sparked major protests and forced the Maltese government to review its abortion law. This paper studies how this process unfolded. We looked at newspapers and political speeches. We wanted to understand the arguments of those fighting for abortion rights and those against them. We found that those fighting for abortion pushed the government to act. But a powerful and well-organised anti-choice movement fought against any changes. The government gave in to pressure from influential conservative and religious groups. The result was a new law that is very restrictive. It only allows an abortion in rare cases to save the pregnant person's life. This change does not provide meaningful access to abortion care. Yet, this is the first time there was a change to Malta's complete ban. This shows that the old rules can change. It creates an important starting point for future work to secure full reproductive rights in Malta.

Although very large wars remain an enduring threat in global politics, we lack a clear understanding of how some wars become large and costly, while most do not. There are three possibilities: Large conflicts begin with intense fighting, accumulate severity over a long duration, or escalate in intensity over time. Using detailed within-conflict data on civil and interstate wars (1946-2008), we show that escalation dynamics-variations in fighting intensity within an armed conflict-are the primary mechanism for producing large conflicts. Civil wars, however, tend to deescalate once they become very large, limiting their overall severity, while interstate wars exhibit a persistent risk of continual escalation. Simple models of within-conflict severity dynamics show that this distinction compactly explains the historical size distributions of civil and interstate wars, and unconditioned escalation is a plausible mechanism for Richardson's law-the power law pattern in the frequency and severity of interstate conflicts. The dynamics of escalation within conflicts have broad implications for conflict theory and risk assessment.

Inadequate access to clinical bacteriology testing in low-resource settings compromises individual patient care and contributes to antimicrobial resistance. Funders, policy makers, and health administrators working to expand bacteriology testing in sub-Saharan Africa require evidence-based guidance. The aim of this study was to assemble a costed consensus list of minimum equipment and consumables required to implement and operate a functional clinical bacteriology laboratory in secondary and tertiary care hospitals in sub-Saharan Africa, to guide funders and health administrators. A consensus list of minimum materials for diagnosing bloodstream infections was assembled by experts from Africa, North America, and Europe, representing academia, funders, and implementers. A modelling study was performed to estimate costs across several testing scenarios developed using a formal framework for forecasting testing volumes and reagent usage. Outcomes assessed were consumable costs per hospital admission and per investigation of septic episode and costs of non-recurring items at the time of establishment of a laboratory. Data from two accredited bacteriology laboratories providing individual patient care in Benin and Ethiopia were used to inform expected positivity rates, reagent usage, and testing volumes. Supplier quotes from North America and Europe were used to provide average unit costs and 95% uncertainty ranges. The estimated mean consumable cost per hospital admission was, in 2023 USD, $6·23 (95% uncertainty range 5·42-7·54) in the strict minimum scenario and $10·86 (9·82-12·31) in the standard scenario. The mean cost for the minimal equipment list at the time of establishment of a laboratory was estimated at $30 763 (28 403-33 043; plus an annual equipment maintenance cost of $3076 [2840-3304]), which includes purchase of commercial quality control strains and other non-recurring consumables. Available data suggest that costs from national distributors in sub-Saharan Africa could be three-fold higher than those described. Finally, we provide a transparent and adaptable basis for estimating minimal testing volumes and reagent usage, enabling tailored procurement planning in regions currently without clinical bacteriology laboratories. These results inform national antimicrobial resistance action plans on supply procurement, costing, and the ability to benchmark and forecast minimal acceptable testing volumes for the diagnosis of bloodstream infections for individual patient care. Fonds de recherche du Québec - Santé.

Background: Psychiatric inpatients may be vulnerable to head trauma; however, associations among psychiatric diagnosis, trauma mechanisms, and acute trauma-related neuroimaging findings among patients requiring neurosurgical consultation remain unclear. Methods: This retrospective observational study included psychiatric inpatients referred for neurosurgical consultation after head trauma at a tertiary neuropsychiatric specialty hospital between July 2022 and December 2025. Psychiatric diagnoses were grouped into psychotic, mood, substance use, organic/symptomatic, and other disorders. Trauma mechanisms were classified as falls, self-harm, assault/fight-related injuries, and other trauma types. Radiological findings were classified as trauma-related abnormalities or secondary incidental findings, including age-related changes. Associations were evaluated using chi-square tests, with false discovery rate correction applied to global and binary comparisons. Exploratory multivariable regression models were used as sensitivity analyses. Results: The cohort comprised 461 psychiatric inpatients who sustained head trauma, underwent radiological imaging, and were referred for neurosurgical consultation. Trauma mechanisms differed significantly across psychiatric diagnostic groups (&#x3c7;2 = 30.89, p = 0.002). Falls were the most common mechanism (189/461, 41.0%). Assault/fight-related trauma showed the clearest diagnosis-associated pattern (&#x3c7;2 = 19.72, p < 0.001, Cram&#xe9;r's V = 0.207) and remained the only significant binary outcome after false discovery rate correction. Acute trauma-related imaging findings were observed in 35 patients (7.6%) and were not associated with psychiatric diagnosis (&#x3c7;2 = 6.16, p = 0.187). Calcifications were the most frequent imaging finding (191/461, 41.4%). Conclusions: In psychiatric inpatients, while head trauma patterns and neuroimaging findings have the potential to be explained by psychiatric diagnoses, they may also reflect unmeasured behavioral and clinical factors.

Young age is an independent risk factor for the development of breast cancer brain metastases (BM). Prior work showed that 17&#x3b2;-estradiol (E2), the predominant premenopausal hormone, promotes BM of tumors intrinsically unresponsive to E2, in part through modulating estrogen receptor-alpha expressing (ER&#x3b1;&#x207a;) glial cells. However, how E2 reshapes the brain tumor microenvironment (TME), particularly microglia&#x2011;mediated immunity, and its impact to BM progression remains unclear. scRNA sequencing and multiparametric flow cytometry were used to define the impact of E2 and E2-suppression on brain immune-cell populations across different stages of BM progression using spontaneous and experimental models of BM. Depletion of microglia and T-cell co-cultures were used to study microglia's role in E2-induced BM. The effects of E2-suppression alone or in combination with whole brain radiotherapy were tested in preclinical models mimicking late-stage BM. E2 repressed immune surveillance and immune activation programs in microglia from early to late stages of brain metastatic progression, suppressing recruitment of effector immune cells to BM. Estrogen suppression, in turn reactivated anti-tumoral signaling in microglia and increased recruitment of effector immune cells to the brain. Microglia from E2-treated BM-bearing mice showed a reduced capacity to promote T-cell expansion, effector potential, and CD8&#x207a;T cell-mediated tumor cell killing. Conversely, E2-suppression reactivated an effective anti-tumoral response and synergized with RT to significantly decrease BM progression. These findings reveal a previously unrecognized mechanism by which E2 accelerates BC&#x2011;BM progression through microglial immunosuppression and support evaluation of endocrine therapies as adjunct treatments for ER&#x207b; breast cancer brain metastases. Brain metastases from breast cancer are especially common in younger women, but the reasons why are unclear. This study investigated how the hormone estrogen (E2) influences the brain&#x2019;s immune environment during metastasis. We found that E2 suppresses microglia-the brain&#x2019;s immune sentinels-and limits the activity and recruitment of cancer&#x2011;fighting T cells. Removing or blocking E2 restored microglial defenses, increased immune cell entry into the brain, and improved the effectiveness of radiation therapy. These findings show that estrogen helps create a brain environment that supports tumor growth and suggest that blocking estrogen may improve treatment even for estrogen-receptor-negative breast cancers.

This paper explores the management of mass casualty incidents in Eastern Ukraine, focusing on the application of the Eight Domains of Mass Casualty Management by the Ukrainian Medical Service. Following the Russian invasion, Ukraine's military and civilian health services have had to adapt to unprecedented casualty rates to prevent overwhelming the healthcare system. The Eight Domains-distribution, decompress, delay, delegate, deliver faster and deliver better, dynamic levels of care, and de-escalation-serve as compensatory mechanisms to manage this chronic major medical incident. The paper highlights the innovative approaches and adaptive strategies employed by the Armed Forces of Ukraine (AFU) Medical Services to maintain effective medical care despite the high demand and constrained resources. The report underscores the importance of international support and continued research to enhance the resilience and capability of the AFU Medical Services in responding to ongoing and future conflicts and proposes future direction for all military medical services to meet the challenges of large scale conflict operations and warfighting at scale.

The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum. We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a "fight-or-flight"-like response.

Due to the deteriorating global security situation, many countries are preparing their health systems for armed conflict. Wartime health care delivery is challenging due to the loss of territorial control and attacks on Emergency Medical Services (EMS). The objectives of this study were to use Emergency Department (ED) data from the hospital closest to the areas of fighting during the October 7, 2023, attacks in Israel, to determine what patient factors relate to status as dead on arrival (DoA), high acuity, and to explore the epidemiology of injury patterns. This is a retrospective cross-sectional cohort study. All patients presenting with injuries from the October 7, 2023, attacks, from 06h30 until 24h00, were included. Variables included demographics, patient classification (civilian or combatant), mode of arrival, condition, injury mechanism and injury location. Two logistic regression models with backward elimination were used to determine the patient factors associated with DoA and high acuity. A total of 301 patients were included. A majority (67.8%) arrived at the ED informally instead of by ambulance (23.9%). A total of 26.6% were DoA. Informal arrival was associated with DoA (OR 10.73, CI [4.18-36.55]). Injuries by firearms and thoracic injuries had higher odds of high acuity (OR 4.15 95% CI [1.67-11.50] and OR 4.35 95% CI [1.49-12.95]), while extremity injuries had lower odds (OR 0.41 95% CI [0.17-0.99]). Firearm-related injuries were more common among combatants compared to civilians (55.3% vs. 35.1%, p&#xa0;&#x2264;&#xa0;0.05). Extremity injuries accounted for more than half of injuries in both civilians and combatants (52.3% vs. 59.5%, p&#xa0;=&#xa0;0.31). In an armed conflict with loss of territorial control and reduced EMS access, healthcare planners may need to anticipate significant prehospital death and that many patients arrive at hospital informally. Prehospital death may be reduced by expanding lay bystander skills in trauma care as these may access patients before ambulances do. Due to survival bias, patients with firearm-related injuries may have more urgent care needs upon reaching hospital than patients with explosion-related injuries. Given the higher survivability of extremity injuries, these may be overrepresented among patients who reach hospital.

The phylum Apicomplexa encompasses a diverse group of protozoan parasites of profound medical and veterinary importance, among which the genera&#xa0;Plasmodium&#xa0;and&#xa0;Babesia&#xa0;stand out because of their shared pathological niche within host erythrocytes. While&#xa0;Plasmodium&#xa0;spp., transmitted by anopheline mosquitoes, are the causative agents of human and zoonotic malaria,&#xa0;Babesia&#xa0;spp., transmitted by ixodid ticks, cause babesiosis, a burgeoning zoonosis and a significant cause of economic loss in the livestock industry. Globally, babesiosis is an emerging threat, with&#xa0;Babesia microti&#xa0;being the primary cause of human babesiosis in the USA and Europe, transmitted by&#xa0;Ixodes scapularis&#xa0;ticks. Although their life cycles diverge critically, most notably in the presence of an exo-erythrocytic hepatic stage in&#xa0;Plasmodium&#xa0;and its absence in&#xa0;Babesia, both parasites share a core pathogenic strategy. They invade, replicate within, and lyse red blood cells, leading to the clinical manifestations of haemolytic anaemia and fever. This review undertakes a comprehensive comparative analysis of&#xa0;Plasmodium&#xa0;and&#xa0;Babesia, leveraging the vast body of research on the former to illuminate the biology and vulnerabilities of the latter. We systematically dissected their parallel life cycles in both vertebrate and invertebrate hosts, elucidating the molecular mechanisms underlying their distinct developmental pathways and transmission strategies. A central focus is placed on the conserved machinery of erythrocyte invasion, a multi-step process mediated by an apical complex of secretory organelles (micronemes and rhoptries) and specific ligand-receptor interactions, which presents a prime target for intervention. Beyond cellular invasion, we delve into the shared metabolic architecture that constitutes the foundation for cross-species drug discovery. We critically evaluated high-value conserved targets, such as the mitochondrial cytochrome&#xa0;bc&#x2081; complex, proteasomal protein degradation system, unique apicoplast organelle with its prokaryotic pathways, essential kinases, and folate biosynthesis pathway, dihydroorotate dehydrogenase (DHODH), ATP4, falcipain proteases, and the heme detoxification pathway. For each target, we discuss the mechanism of action of existing and experimental inhibitors, the evidence for their efficacy across both genera, and the emerging challenge of drug resistance. Ultimately, this synthesis argues that the deep evolutionary relationship between&#xa0;Plasmodium&#xa0;and&#xa0;Babesia&#xa0;has resulted in a core set of indispensable biological processes that are susceptible to parallel therapeutic interventions. By mapping the shared vulnerabilities within their erythrocytic pathogenesis, this review will be useful in designing novel, broad-spectrum antiprotozoal agents and strategic drug repurposing efforts, thereby advancing the fight against both malaria and babesiosis.

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host-pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers.